Cytogen Corporation

Elan Corporation, Plc

Other

Eusa Pharma Ltd.

Ultee, Michiel E.

Alvarez, Vernon L.

Vernon L Alvarez

Daniel J Coughlin

Benjamin A Belinka, Jr

Daniel Joseph O'Mahony

John D Rodwell

Thomas J McKearn

Richard Wood

Imelda Lambkin

Gerard M Cagney

John W Goers

Chyi Lee

John M Carter

Judith Singleton

Catherine A Patterson

Michela Seveso

Hurley D King

Richard C Siegel

Michiel E Ultee

Robert D Radcliffe

Benjamin A Belinka

A method of identifying a peptide which permits or facilitates the transport of an active agent through a human or animal tissue. A predetermined amount of phage from a random phage library or a preselected phage library is administered in vivo or in situ to a site in an animal, such as into the gastro-intestinal tract. At a predetermined time, the phage which is transported across a tissue barrier is harvested at a harvesting site, such as in portal or systemic blood or brain tissue, which is separated from the site of administration by the tissue barrier to select transported phage. This transported phage is amplified in a host. This cycle of events is repeated (using the transported phage produced in the most recent cycle) a predetermined number of times to obtain a selected phage library containing phage which can be transported from the site of administration to the harvesting site. The identity of at least one peptide coded by phage in the selected phage library is determined to identify a peptide which permits or facilitates the transport of an active agent through a human or animal tissue.

Peptides which enhance transport across tissues and methods of identifying and using the same

This invention relates to proteins (e.g., peptides) that are capable of facilitating transport of an active agent through a human or animal gastro-intestinal tissue, and derivatives (e.g., fragments) and analogs thereof, and nucleotide sequences coding for said proteins and derivatives. The proteins of the invention have use in facilitating transport of active agents from the lumenal side of the GIT into the systemic blood system, and/or in targeting active agents to the GIT. Thus, for example, by binding (covalently or noncovalently) a protein of the invention to an orally administered drug, the drug can be targeted to specific receptor sites or transport pathways which are known to operate in the human gastrointestinal tract, thus facilitating its absorption into the systemic system.

Random peptides that bind to gastro-intestinal tract (GIT) transport receptors and related methods

This invention relates to proteins (e.g., peptides) that are capable of facilitating transport of an active agent through a human or animal gastrointestinal tissue, and derivatives (e.g., fragments) and analogs thereof, and nucleotide sequences coding for said proteins and derivatives. The proteins of the invention have use in facilitating transport of active agents from the lumenal side of the GIT into the systemic blood system, and/or in targeting active agents to the GIT. Thus, for example, by binding (covalently or noncovalently) a protein of the invention to an orally administered drug, the drug can be targeted to specific receptor sites or transport pathways which are known to operate in the human gastrointestinal tract, thus facilitating its absorption into the systemic system.

Abtides are provided. Abtides are peptides identified by a two-step process of screening random peptide libraries. In the first step, the target ligand is an antibody or receptor (or derivative thereof). The peptides identified in the first screening step are used as target ligands in the second screening step. The peptides identified in the second screening step are abtides. Abtides possess binding specificities that are similar to the binding specificities of the antibodies or receptors that are used in the first screening step. Abtides may be used in place of antibodies in many assays or therapeutic applications. Abtides binding to polymorphic epithelial mucin (PEM) are provided. Also provided are methods of obtaining abtides as well as diagnostic and therapeutic compounds containing abtides.

Antigen binding peptides (abtides) from peptide libraries

The invention relates to a method of treating a patient in need thereof, including a need for diagnosis or treatment, comprising the administration of a metal complex of a polypeptide construct. The construct comprises a compound of the formula (I): ##STR1## in which, 'B' is a hydrocarbon backbone,

Treatment methods using metal-binding targeted polypeptide constructs

This invention relates to the preparation and use of novel open-chain or cyclic polypeptide constructs in which two or more polypeptide chains, in an open-chain construct, or one or more chains, in a cyclic construct, are chemically derivatized such that the resulting construct exhibits both metal-binding capability and tissue-, organ- or cell-targeting selectivity. In particular, the polypeptide constructs of the present invention comprise compounds of the formula (I): ##STR1## in which, 'B' is a hydrocarbon backbone, 'P' is a polypeptide capable of targeting particular cells, tissues or organs of the body, 'A' may be the group --NR'--NR'-- or the group --NR'--NR'--L-- in which L may be an aliphatic or aromatic linker group, R, R', and R' may be the same or different and may be hydrogen or an aliphatic group, m is an integer.gtoreq.2, provided that the groups R, R', R', L and 'P' of a given chain may be the same or different from the groups R, R', R', L and 'P' of another chain, n is an integer.gtoreq.0; or a pharmaceutically acceptable salt thereof. The constructs of the present invention are capable of binding a variety of metallic species.

Metal-binding targeted polypeptide constructs

This invention relates to the preparation and use of novel open-chain or cyclic polypeptide constructs in which two or more polypeptide chains, in an open-chain construct, or one or more chains, in a cyclic construct, are chemically derivatized such that the resulting construct exhibits both metal-binding capability and tissue-, organ- or cell-targeting selectivity. In particular, the polypeptide constructs of the present invention comprise compounds of the formula (I): ##STR1## in which, 'B' is a hydrocarbon backbone, 'P' is a polypeptide capable of targeting particular cells, tissues or organs of the body, 'A' may be the group --NR'--NR'-- or the group --NR'-- NR'--L-- in which L may be an aliphatic or aromatic linker group, R, R', and R' may be the same or different and may be hydrogen or an aliphatic group, m is an integer.gtoreq.2, provided that the groups R, R', R', L and 'P' of a given chain may be the same or different from the groups R, R', R', L and 'P' of another chain, n is an integer.gtoreq.0; or a pharmaceutically acceptable salt thereof. The constructs of the present invention are capable of binding a variety of metallic species.

This invention relates to the preparation and use of novel open-chain or cyclic polypeptide constructs in which two or more polypeptide chains, in an open-chain construct, or one or more chains, in a cyclic construct, are chemically derivatized such that the resulting construct exhibits both metal-binding capability and tissue-, organ- or cell-targeting selectivity. In particular, the polypeptide constructs of the present invention comprise compounds of the formula (I): ##STR1## in which, 'B' is a hydrocarbon backbone, 'P' is a polypeptide capable of targeting particular cells, tissues or organs of the body, 'A' may be the group --NR'--NR'-- or the group --NR'--NR'--L-- in which L may be an aliphatic or aromatic linker group, R, R' and R' may be the same or different and may be hydrogen or an aliphatic group, m is an integer .gtoreq.2, provided that the groups R, R', R', L and 'P' of a given chain may be the same or different from the groups R, R', R', L and 'P' of another chain, n is an integer .gtoreq.0; or a pharmaceutically acceptable salt thereof. The constructs of the present invention are capable of binding a variety of metallic species.

A system or method for identifying and/or designing novel peptides and polypeptides comprising an amino acid sequence which mimics the molecular recognition site of either (a) a macromolecule such as an immunoglobulin, an enzyme, a receptor protein, a lectin or other binding protein or (b) a small molecule or a small region of a large molecule which functions as a ligand and is recognized and binds specifically to a macromolecule is disclosed. Novel peptides and polypeptides as well as conjugates of the peptides and polypeptides are also disclosed. Applications for use of the peptides, polypeptides and conjugates in a wide range of fields such as biomedicine; biological control and pest regulation; agriculture; cosmetics; environmental control and waste management; chemistry; catalysis; nutrition and food industries; military uses; climate control, etc. are disclosed.

Molecular recognition units

The invention relates to amine-containing porphyrin derivatives. Theporphyrins can be used as photosensitizers which are useful as therapeutic agents. Also described are methods for preparing conjugates in which a porphyrin derivative is covalently attached to an antibody or antibody fragment. In vivo therapeutic methods utilizing the conjugates are also desired.

Amine-containing porphyrin derivatives

Radiohalogenated compounds which are useful as intermediates for preparing radiohalogenated antibody conjugates in which the radiohalogenated compound is site specifically attached to an oxidized carbohydrate moiety of an antibody or antibody fragment are disclosed. Methods for making the compounds and the antibody conjugates as well as methods of use of the same are also disclosed In particular, phenolic hydrazide and phenolic amine compounds are disclosed.

Radiohalogenated compounds for site specific labeling

A novel method for preparing soluble antibody fragment compositions having superior characteristics for targeted delivery when administered in vivo are disclosed. The antibody fragment compositions are characterized by substantially the same immunospecificity as the unconjugated antibody and aqueous solubility such that they are suitable for in vivo administration. Therapeutic and diagnostic methods utilizing the antibody fragment compositions are also disclosed.

Growing community of inventors

Morrisville, PA, United States of America

Vernon L Alvarez